Cell Journal (Yakhteh)
Volume:26 Issue: 2, Feb 2024

Exposure to phosgene, a colourless poisonous gas, can lead to various health issues including eye irritation, a dry and burning throat, vomiting, coughing, the production of foamy sputum, difficulty in breathing, and chest pain. This systematic review aims to provide a comprehensive overview of the clinical manifestations and treatment of phosgene toxicity by systematically analyzing available literature. The search was carried out on various scientific online databases to include related studies based on inclusion and exclusion criteria with the use of PRISMA guidelines. The quality of the studies was assessed using the Mixed Methods Appraisal Tool (MMAT). Thirteen articles were included in this study after the screening process. Inhalation was found to be the primary health problem of phosgene exposure with respiratory symptoms such as coughing and dyspnea. Chest pain and pulmonary oedema were also observed in some cases. Furthermore, pulmonary crackle was the most common reported physical examination. Beyond respiratory tract health issues, other organs involvements such as cardiac, skin, eye, and renal were also reported in some studies. The symptoms can occur within minutes to hours after exposure, and the severity of symptoms depends on the amount of inhaled phosgene. The findings showed that bronchodilators can alleviate symptoms of bronchoconstriction caused by phosgene. Oxygen therapy is essential for restoring oxygen levels and improving respiratory function in cases of hypoxemia. In severe cases, endotracheal intubation and invasive mechanical ventilation are used for artificial respiration, along with the removal of tracheal secretions and pulmonary oedema fluid through suctioning as crucial components of supportive therapy.

Kidney-liver crosstalk plays a crucial role in normal and certain pathological conditions. In pathologic states, both renal-induced liver damage and liver-induced kidney diseases may happen through these kidney-liver interactions. This bidirectional crosstalk takes place through the systemic conditions that mutually influence both the liver and kidneys. Ischemia and reperfusion, cytokine release and pro-inflammatory signaling pathways, metabolic acidosis, oxidative stress, and altered enzyme activity and metabolic pathways establish the base of this interaction between the kidneys and liver. In these concomitant kidney-liver diseases, the survival rates strongly correlate with early intervention and treatment of organ dysfunction. Proper care of a nephrologist and hepatologist and the identification of pathological conditions using biomarkers at early stages are necessary to prevent the complications induced by this complex and potentially vicious cycle. Therefore, understanding the characteristics of this crosstalk is essential for better management. In this review, we discussed the available literature concerning the detrimental effects of kidney failure on liver functions and liver-induced kidney diseases.

The aim of this study was to synthesize chitosan nanoparticles (Cs NPs) for resveratrol (RSV) delivery and assess their effectiveness in inducing autophagy in MDA-MB 231 cells.

In this experimental study, Pure and RSV-loaded Cs NPs (RSV. Cs NPs) were prepared via the ionic gelation method, and their physicochemical properties were characterized using standard techniques, and RSV release was measured in vitro. MDA-MB 231 cells were incubated with RSV, Cs NPs, and RSV. Cs NPs and Half-maximal inhibitory concentration (IC50) values were calculated following the MTT test. Cell viability was assessed by lactate dehydrogenase (LDH) assay, and autophagy was evaluated using the real-time polymerase chain reaction (PCR).

NP formation was confirmed with the analysis of FTIR spectra. Pure and RSV. Cs NPs had 36.7 and 94.07 nm sizes with 18.3 and 27 mV zeta potentials, respectively. Above 60% of RSV entrapped within NPs was released in an initial burst manner followed by a gradual release till 72 hours. Cs and RSV. Cs NPs restrained cell proliferation at lower concentrations. RSV. Cs NPs showed the highest anticancer effect and stimulated autophagy, indicated by increased Beclin-1 ATG5, ATG7, LC3A, and P62 expression.

RSV. Cs NPs show promising effects in inhibiting invasive breast cancer (BC) cells in vitro by inducing autophagy.

Enhanced cell survival and drug resistance in tumor cells have been linked to the overexpression of antiapoptotic members of the Bcl-2 family proteins, including Bcl-2 and Mcl-1. The aim of this study was to explore the impact of formononetin and dihydroartemisinin combination on the growth and apoptosis of acute myeloid leukemia (AML) cells.

In this experimental study, the cell survival and cell proliferation were tested by MTT assay and trypan blue staining. The evaluation of cell apoptosis was conducted using Hoechst 33342 staining and a colorimetric assay to measure caspase-3 activity. To determine the mRNA levels of Mcl-1, Bcl-2, Bax, and Cyclin D1, a quantitative real-time polymerase chain reaction (qRT-PCR) was performed.

We showed that treatment with either formononetin or dihydroartemisinin alone, led to significant decrease in the cell survival and growth, and triggered apoptosis in U937 and KG-1 AML cell lines. Moreover, treatment with each of the compounds alone significantly decreased the mRNA levels of Mcl-1, Bcl-2 and Cyclin D1 mRNA, while, the expression level of Bax mRNA was enhanced. Combination of two compounds showed a synergistic anti-cancer effect.

The anti-leukemic potential of formononetin and dihydroartemisinin is exerted through the effect on cell cycle progression and intrinsic pathway of apoptosis. Therefore, they can be considered as a potential anti-leukemic agent alone or along with existing chemotherapeutic drugs.

Mesenchymal stem cells (MSCs) are widely recognized as a promising cell type for therapeutic applications due to their ability to secrete and regenerate bioactive molecules. For effective bone healing, it is crucial to select a scaffold that can support, induce, and restore biological function. Evaluating the scaffold should involve assessing MSC survival, proliferation, and differentiation. The principal aim of this investigation was to formulate composite nanofibrous scaffolds apt for applications in bone tissue engineering.

In this experimental study, nanofibrous scaffolds were fabricated using Poly-L-lactic acid (PLLA) polymer. The PLLA fibers’ surface was modified by integrating collagen and hydroxyapatite (HA) nanoparticles.

The findings demonstrated that the collagen- and nanohydroxyapatite-modified electrospun PLLA scaffold positively influenced the attachment, growth, and osteogenic differentiation of MSCs.

Coating the nanofiber scaffold with collagen and nanoparticle HA significantly enhanced the osteogenic differentiation of MSCs on electrospun PLLA scaffolds.

Acute lymphoblastic leukemia (ALL) is a highly heterogeneous leukemia. Despite the current improvement in conventional chemotherapy and high survival rates, the outcomes remain challenging. Sesquiterpen extracted from the Tanacetum parthenium, parthenolide, is a potential anticancer agent that can modulate the expression of miRNAs and induce apoptosis. The objective of this study was to investigate the effect of parthenolide in combination with vincristine and alone on the apoptosis rate and expression of miR-125b-5p, miR-181b-5p, and miR-17-5p in the NALM6 cell line.

In this experimental study, cell viability and metabolic activity were determined through MTT assay and PI staining. Flow cytometry was applied to evaluate the rate of apoptosis. The expression of miRNAs was assessed using real-time polymerase chain reaction. Bioinformatic analyses, including Cytoscape, RNAhybrid, and signaling pathway analysis were employed to investigate the association of miR-17-5p, miR-181b-5p and miR-125b- 5p with apoptosis. Further, molecular docking served to validate the modulation of these miRNAs by parthenolide and vincristine treatment.

The MTT assay indicated that 7.7 μM of parthenolide decreased the metabolic activity to 50% after 48 hours. PI staining analysis indicated that at concentrations below the half maximal inhibitory concentration, parthenolide caused 50% cell death. Flow cytometric analysis indicated that parthenolide (1.925 μM) in combination with vincristine (1.2 nM) induced apoptosis in 83.2% of the cells. Real-time quantitative reverse transcription polymerase chain reaction (qRTPCR) analysis showed significant changes in the expression levels of miR-17-5p, miR-125b-5p, and miR-181b-5p. Moreover, the combination therapy downregulated the expression of miRNAs significantly. This was consistent with our bioinformatic analysis demonstrating that the studied miRNAs are regulators of apoptosis. Finally, molecular docking validated the modulation of the miRNAs by parthenolide and vincristine.

Parthenolide in combination with vincristine triggers apoptosis at a high rate in the NALM6 cell line. Moreover, this combination therapy can decrease the expression of miR-17-5p, miR-181b-5p, and miR-125b-5p.

There is interest in using cytotoxic T lymphocyte antigen-4 (CTLA-4) immunotherapy to treat blood cancers. Unfortunately, patients with acute lymphoblastic leukaemia (ALL) frequently exhibit resistance to treatment and natural killer (NK) cell exhaustion. This study aims to increase the cytotoxic potency of natural killer cells by using CTLA-4 to block the Nalm-6 leukaemia cell line.

In this experimental study, NK cells were purified from the peripheral blood mononuclear cells (PBMCs) of 10 healthy people and assessed by flow cytometry for purity and viability. The purified cells were activated overnight at 37°C and 5% CO2 with interleukin-15 (IL-15, 10 ng/ml) followed by evaluation of expressions of CTLA-4, activating and inhibitory receptors, and the release of interferon gamma (IFN-γ) and granzyme B (GZM B). CTLA-4 expression on NK cells from recurrent ALL patients was also evaluated. Finally, the cytotoxic activity of NK cells was assessed after the CTLA-4 blockade.

The purity of the isolated cells was 96.58 ± 2.57%. Isolated NK cells activated with IL-15 resulted in significantly higher CTLA-4 expression (8.75%, P<0.05). Similarly, CTLA-4 expression on the surface of NK cells from patients with ALL was higher (7.46%) compared to healthy individuals (1.46%, P<0.05). IL-15 reduced NKG2A expression (P<0.01), and increased expressions of NKP30 (P<0.05) and NKP46 (P<0.01). The activated NK cells released more IFN-γ (P<0.5) and GZM B (P<0.01) compared to unactivated NK cells. Blockade of CTLA-4 enhanced the NK cell killing potential against Nalm-6 cells (56.3%, P<0.05); however, IFN-γ and GZM B levels were not statistically different between the blocked and non-blocked groups.

Our findings suggest that CTLA-4 blockage of Nalm-6 cells causes an increase in antitumour activity of NK cells against these cells. Our study also provides evidence for the potential of cancer immunotherapy treatment using blocking anti-CTLA-4 mAbs.

According to the response-to-retention hypothesis, the inception of atherosclerosis is attributed to the deposition and retention of lipoprotein in the arterial intima, facilitated by altered proteoglycans with hyperelongated glycosaminoglycan (GAG) chains. Recent studies have elucidated a signaling pathway whereby transforming growth factor-β (TGF-β) promotes the expression of genes linked to proteoglycan GAG chain elongation (CHSY1 and CHST11) via reactive oxygen species (ROS) and the downstream phosphorylation of ERK1/2 and Smad2L. Atorvastatin is known to exhibit pleiotropic effects, including antioxidant and anti-inflammatory. The purpose of the present research was to ascertain the influence of atorvastatin on TGF-β-stimulated expression of CHST11 and CHSY1 and associated signaling pathways using an in vitro model.

In this experimental study, vascular smooth muscle cells (VSMCs) were pre-incubated with atorvastatin (0.1-10 μM) prior to being stimulated with TGF-β (2 ng/ml). The experiment aimed to evaluate the phosphorylation levels of Smad2C, Smad2L, ERK1/2, the NOX p47phox subunit, ROS production, and the mRNA expression of CHST11 and CHSY1.

Our research results indicated that atorvastatin inhibited TGF-β-stimulated CHSY1 and CHST11 mRNA expression. Further experiments showed that atorvastatin diminished TGF-β-stimulated ROS production and weakened TGF-β-stimulated phosphorylation of p47phox, ERK1/2, and Smad2L; however, we observed no effect on the TGF-β- Smad2C pathway.

These data suggest that atorvastatin demonstrates anti-atherogenic properties through the modulation of the ROS-ERK1/2-Smad2L signaling pathway. This provides valuable insight into the potential mechanisms by which atorvastatin exerts its pleiotropic effects against atherosclerosis.

In this article published in Cell J, Vol 19, No 4, Jan-Mar (Winter) 2018, on pages 654-659, the authors found that Figures 2 and 3 had some errors that accidentally happened during organizing figures. Because of mislabeling some images and saving them in an incorrect folder, the following figures' legends are corrected.
The authors would like to apologize for any inconvenience.